Ultra high throughput microfluidic analytical systems and methods

Abstract

Analytical systems and methods that use a modular interface structure for providing an interface between a sample substrate and an analytical unit, where the analytical unit typically has a particular interface arrangement for implementing various analytical and control functions. Using a number of variants for each module of the modular interface structure advantageously provides cost effective and efficient ways to perform numerous tests using a particular substrate or class of substrates with a particular analytical and control systems interface arrangement. Improved optical illumination and detection system for simultaneously analyzing reactions or conditions in multiple parallel microchannels are also provided. Increased throughput and improved emissions detection is provided by the present invention by simultaneously illuminating multiple parallel microchannels at a non-normal incidence using an excitation beam including multiple excitation frequencies, and simultaneously detecting emissions from the substances in the microchannels in a direction normal to the substrate using a detection module with multiple detectors.

1. A microfluidic system comprising:
 a modular interface structure comprising at least first and second modules that provide an interface between an analytical instrument and a microscale substrate, wherein said first module comprises a heater interface which is positioned below the microscale substrate and is configured to heat fluid in one or more wells or a channels of microscale substrate; and  
 wherein said second module is spatially separated from said first module and is configured to interface with an analytical instrument and the first module, the second module comprising a fluid control interface which is configured to control the movement of fluid in one or more channels of the microscale substrate.  
 
     
     
       2. The system of  claim 1 , wherein the heater interface is positioned to simultaneously contact two or more microscale channels of the substrate. 
     
     
       3. The system of  claim 1 , wherein the heater interface is configured to contact the microscale substrate from an underside of the microscale substrate, while permitting one or more capillaries on the underside of the microscale substrate to project downward from the microscale substrate. 
     
     
       4. The system of  claim 1 , wherein the first module comprises a microscale substrate holder that supports the microscale substrate above the heater interface. 
     
     
       5. The system of  claim 4 , wherein the holder consists of one or more of: a polymer, polymethylmethacrylate, polycarbonate, polytetrafluoroethylene, polyvinylchloride, polydimethylsiloxane, polysulfone, polystyrene, polymethylpentene, polypropylene, polyethylene, polyvinylidine, and acrylonitrile-butadiene-styrene copolymer. 
     
     
       6. The system of  claim 1 , further comprising an excitation or illumination source and a detector array. 
     
     
       7. The system of  claim 6 , wherein the illumination source includes two or more lasers. 
     
     
       8. The system of  claim 7 , wherein the illumination source comprises illumination optics that combine one or more output from two or more of the lasers. 
     
     
       9. The system of  claim 1 , further comprising a robotic armature for moving the microscale substrate. 
     
     
       10. The system of  claim 1 , further comprising an automatic refilling module configured to deliver fluid to the one or more wells. 
     
     
       11. The system of  claim 1 , wherein the second module comprises locating pins or holes which are configured to mate with corresponding holes or pins located on or within the first module. 
     
     
       12. The system of  claim 1 , wherein the second module comprises an electrical interface connector that is configured to mate with a corresponding electrical connector associated with the analytical instrument. 
     
     
       13. The system of  claim 1 , wherein the second module comprises a vacuum or pressure port for supplying one or more of a vacuum or pressure to one or more wells or channels of the microscale substrate. 
     
     
       14. The system of  claim 1 , wherein the second module comprises a window or opening defined therein to allow light to pass therethrough. 
     
     
       15. The system of  claim 1 , wherein the fluid control interface of the second module comprises a plurality of electrode pins which are configured to interface with a plurality of wells of the microscale substrate.